Clearance of xenobiotics from rivers

Chemosphere,Vol. 39, No. 3, pp.407-417, 1999

Pergamon

© 1999 Elsevier Science Ltd. All rights reserved 0045-6535/99/$ - see front matter

PII: S0045-6535(99)00004-1

CLEARANCE OF XENOBIOTICS FROM RIVERS G e o r g K a r l a g a n i s A, S t a n l e y E. B r a d l e y B, M a n f r e d Spreafico c

AFederal Office of Environment, Forests and Landscape, CH-3003 Berne, Switzerland BDepartment of Clinical Pharmacology, University of Berne, CH-3010 Berne, Switzerland CNational Hydrological and Geological Survey, CH-3003 Berne, Switzerland (Received in Germany 9 September 1998; accepted 7 December 1998)

ABSTRACT The aim of this paper was to apply the concept of clearance to the elimination of a xenobiotic (e.g. sodium fluoresceine) from the section of a river. This concept was tested using three different field experiments in the river Aare (1994) and in the river Rhine (1988, 1989) and two different methods of calculation. Median clearance values of sodium fluoresceine cleared from these rivers ranged from 193 to 1011 m3/sec. It is concluded that the clearance concept used in medicine can also be applied to calculate the clearance of xenobiotics from rivers. However, more data are necessary to further evaluate this concept. ©1999 Elsevier Science Ltd. All rights reserved

INTRODUCTION "Clearance" is a widely used expression in medicine, especially in physiology, nephrology, hepatology, pharmacology and clinical pharmacology (1-3). It may be defined as the hypothetical volume of blood plasma that is completely cleared of a solute in a unit of time and is usually expressed in ml/min. The term "clearance" was first introduced in 1928 by Donald D. Van Slyke et al. (4) in human subjects as follows: Urea clearance (ml/min) = Uu. V/Bu Uu was the concentration of urea in urine (mmol urea per ml urine), Bu the concentration of urea in blood (mmol urea per ml blood) and V the urine flow (ml urine per min). This urea clearance was considered equivalent to a hypothetical volume of blood from which urea is "cleared" completely each minute. Urea, a product of protein breakdown, does not degrade in the body and since it must be removed by renal excretion 407

408 it accumulates in the blood during severe renal damage to reach high levels (uraemia) in association with diminished clearance values. It is a useful tool for measuring renal function and for diagnosis of renal insufficiency, since clearance tends to fall before the first clinical signs of failure of kindney failure. The clearance concept is also applied to describe the removal of drugs from the human body. Here the difficulty of maintaining constant blood levels is circumvented by measuring the area under the drug concentration in the blood over the period between its first appearance in and total disappearance from the blood. This value divided into the total dose (D) administered intravenously is equal to the clearance: Drug clearance (ml/min) = D/AUC

,~.

GERMANY

Injection A ~--,'-~..T/ / "rra~er~..~ So~lOthum K /

a,.,~.. "-~

~~

Berne

~ ~

~? ~

)

Figure 1: Sites of sampling after the marker experiment with sodium fluoresceine in the river Aare in March 1994. Clearance calculations have been used in medicine for many years in hospitals all over the world on a routine basis. The clearance concept is simple to use, since it is independent of complicated model calculations. There are many computer programs available which describe the fate of xenobiotics in the environment by simulation of a model. In contrast, there is a lack of methods which are model-independent (5), simple and easy to use also for non-specialists such as governmental agencies. In previous publications the clearance concept has been applied to describe the removal of the xenobiotic atrazine from soil (6,7). Aim of The present study is to apply the clearance concept to the water compartment. Clearance of sodium fluoresceine from a river has been chosen as an example. In analogy to the urea clearance, the

409 River clearance (m3/sec) = E.Q/M is defined by the concentration of sodium fluoresceine (E;mg/m3) at the end of the section of a river multiplied by the flow (Q, m3/sec) of the river divided by the mean concentration of sodium fluoresceine (M; mg/m3) in the part of the river which is described. In analogy of the formula for the drug clearance, it is possible to calculate the river clearance by a second method: River clearance (m3/sec) = L/AUC L means the load of a xenobiotic in a field experiment, e.g. 150 kg of sodium fluoresceine. AUC is the area under the xenobiotic concentration time curve measured at a distinct place along the river during the whole period of the experiment (units sodium fluoresceine concentration mg/m3; time sec). Such a clearance reflects the removal of a xenobiotic from a river section. This new approach is presented herewith and examined with data sets of sodium fluoresceine from three field experiments in Switzerland.

METHODS

c [mg/m~

6--@ 54321 I

0

3000

J

I

I

4OOO

5000

6000

t [min]

Figure 2: Concentration time curve (AUC) of samples containing sodium fluoresceine taken at the "Rhine entrance" during the field experiment in the river Aare in March 1994. This is an example of the data which are used for calculation of the AUC.

410 The concept proposed in this paper was tested using data from three different field experiments in the river Aare (March 1994, Table 1) and in the river Rhine (September 1988, Table 2; July 1989, Table 3). These field experiments were performed by the National Hydrological and Geological Survey. The sites of sampling of one field experiment are depicted in Figure 1. For the first set of calculations the input data were E, Q and M as described above, given in Tables 1-3. For the second set of calculations the input date were L and AUC. AUC (area under the concentration time curve) was calculated by the trapezoidal rule using pairs of data from the field experiments: concentration of sodium fluoresceine (mg/m3) and time after start of the experiment. These concentration and time data were determined at 11, 9, and 13 different places, respectively (Tables 1-3). An example of such a concentration time curve is given in Figure 2. AUC calculations were made with the help of the computer program MATHLAB; the algorithm "trapz" was used.

RESULTS AND DISCUSSION

12,.,_ [ ,i "

g8 C 0 c

8 4 c 0

~

2

T i m e (flours)

ou

zu

Figure 3: Three-dimensional plot of the field experiment in the river Aare in March 1994. Parameters: concentration of sodium fluoresceine (rag/m3), time after the start of the field experiment (hours), distance from the point where the load of sodium fluoresceine was applied.

140.6

Rhine entrance (bridge)

Laufenburg (power station)

19.7

9.9

7.7

1.0

15.2

21.6

48.0

69.33

63.16

58.33

56.5

56.33

784

384

392

222

222

208

2.3

5.7

6.7

12.4

8.6

19.3

4.0

6.2

9.6

10.5

14.0

23.7

(L): 150 kg (= 150.106 mg); Marker point: Bridge Bri.igg/Aegerten

120.9

Paul Scherrer Institute (bridge)

‘1estimated; Load of sodium fluoresceine Marker time: 21 March 1994 12.00 a.m.

103.3 111.0

Brugg (bridge)

87.1 102.3

from the river Aare (March 1994)

Biberstein (bridge)

Clearance of sodium fluoresceine

Brugg (NADUF-Station)

Table 1

169

106

loa

106

106

. 106

185.6;

0.0462.106

0.117.

0.120.

0.225.

0.170.

0.303

(below Biel), Aare-km

451

353

274

262

136

3250

882

UAUC

(2) (m3/sec) =

Cl

1

1

412 Figure 3 and Table 1 reflect the field experiment performed in March 1994 in the river Aare. The experiment lasted about three days. The flow of river between Arch and Well increased from 161 to 794 m3/sec due to the influx of several other rivers. In contrast, the concentration of the marker substance sodium fluoresceine decreased from 128.8 to 1.0 mg/m 3. The end concentration E was always lower than the mean concentration M of each river segment. Clearance values C1 (1) calculated by the method E.Q/M increased from 104 to 481 m3/sec (median 193). AUC decreased from 0.852.106 to 0.0462.106 sec.mg/m 3, which reflects the dilution of the marker substance sodium fluoresceine within the three days of the experiment. Clearance values C1 (2) calculated by the method L/AUC increased from 176 to 3250 m3/sec (median 495). Comparison of Cl (i) with Cl (2) shows corresponding values, differing by a factor between 1.7 and 6.7. These values are in the same order of magnitude, in view of the large scale of the field experiment over a length of 190 kin. It is concluded that the two methods C1 (1) and C1 (2) can be used independent of each other, according to the availability of input data.

E tO

e=

8t O

o

rime

(hours)

--

lO

Figure 4: Three-dimensional plot of the field experiment in the river Rhine in September 1988.

Clearance of sodium fluoresceine

50.3

Birsfelden (power station, below)

66.3

13.3

698

17.7

17.6

I685

I 30.5

15.7

I 7.7 I685

I 28.5

13.3

16.8

I 10.3

698

20.7

I 12.9

23.00

I698

698

I698

38.1

55.2

712 712

34.8

712

17.65

I 10.5

15.1

114.9

15.3

I 16.8

29.4

30.4

38.9

28.7

126.2

I 29.8

1712

109.9

1162.0 130.1

37.6

1141.7

I 300.0’) 1146.8

122.6

1712

1182.2 1111.4

7.9

18.50 18.50

7.6

I 16.00

13.5

6.67

6.33

6.67

17.00

17.00

712

I712

12.83 4.00

I712

17.6

I 4.8

I

I712

13.00

12.08

1988)

1)estimated; Load of sodium fluoresceine (L): 235 kg (= 235.106 mg); Marker point: Albbruck (Germany), Rhine-km 113.5; Marker time: 27 September 1988 07.00 a.m.

Kembs (power station, left side, below)

60.6

42.4

Wyhlen (power station, below)

left side)

42.4

Augst (Dower station, below)

Villaee-Neuf (NADUF-station,

34.8

Rheinfelden (water mark. left side)

30.0

0.9

16.7

(bridge, first pass, german side)

Stein-Sackingen

(Rower station, below)

0.9

16.7

(bridge, middle)

Stein-Sackingen

Riburg-Schwbrstadt

0.9

IO.9

16.7 16.7

15.8

S&zkingen (power station, fish stairs)

(bridge, first pass, Swiss side)

1.2 Il.3

8.5

Laufenburg (lock)

Stein-Sackingen (bridge, left Swiss side)

Il.2

8.5

Stein-Sackingen

Il.2

8.5

Laufenburg (old NALXJF-station)

Il.3

1.3

I

fiom the river Rhine (September

Laufenburg (bridge. tieht eerman side)

Laufenburg (bridge, left Swiss side)

Sampling point

Table 2

106

106

106

106

10.119.

106

lo.115. 106

0.180.

10.196.

10.195.106

10.257. 0.212.

10.223.

I 0.430.106

11676

I 1734

1114

I1021

I1024

I779 943

I 897

1465

Outflow of sewage treatment plant,

681

502

615

787

807

863 1010

810

432

1

I

1

I

I

I

414 The field experiment in the River Rhine in September 1988 (Figure 4, Table 2) was performed during 30 hours over a distance of 66 km. The flow over this segment was rather constant (712 - 685 m3/sec). The concentration of the tracer decreased from 187.3 to 7.6 mg/m3. Median clearance values were 615 (C11) and 1011 m3/sec (C12), respectively. The field experiment in the river Rhine in July 1989 (Figure 5, Table 3) lasted 38 hours over a distance of 16 km. The flow of this segment doubled almost from 580 to 1114 m3/sec. The concentration of the tracer ranged from 313.6 to 2.2 mg/m3. Median clearance values were 474 (Cll) and 876 (C12), respectively. A high clearance value could indicate a short half life of the xenobiotic in this part of the river. However, in humans this is not always the case, since xenobiotics are sometimes bound to proteins (like albumin), and a new variable, the volume of distribution (Vd), was introduced. Clearance (CI), half life (tl/2) and volume of distribution (Vd) are interrelated. First order kinetics and a one-compartment model are consistent with the following equation: C1 ~ 0.693 V d / t l / 2 The volume of distribution Vd is a hypothetical value assuming an ideal equal distribution of the xenobiotic in a hypothetical volume (3). In humans this value is dependent among others on the extent of protein binding of the xenobiotic. A high clearance value cannot necessarily be attributed only to a short half life, but also to a high volume of distribution.

E tO

t-

O ¢.)

Time (hours)

60

Figure 5: Three-dimensional plot of the field experiment in the river Rhine in July 1989.

34.7 34.7 42.8

Zurzach (bridge, middle)

Zurzach (bridge, right)

Koblenz (bridge, middle)

105.1 121.0

Birsfelden (power station)

Kembs/power station)

15.9

8.0

12.4

14.2

7.3

: 13.1

7.3

7.3

7.3

8.1

3.4

3.4

3.4

7.2

7,2

4.2

4.2

4.2

4.2

4.2

4.2

4.2

7.4

7.4

8.3

8.3

37.5

32.5

29.5

25.67

20.33

18.50

15.83

15.I7

16.33

13.33

12.00

12.00

12.17

1.25

1.58

8.17

7.75

8.08

8.17

6.58

7.33

6.50

4.58

4.25

4.25

1.67

1.50

1.33

1.33

1086

1086

1086

1114

I 114

1114

1114

1114

1I 14

590

590

590

590

590

590

584

584

584

584

584

584

584

584

584

584

580

580

580

580

2.2

5.5

7.9

7.9

10.2

11.9

5.0

6.0

16.7

29.2

34.0

35.8

28.8

41.8

38.0

38.0

34.3

17.1

38.3

85.4

54.0

81.8

81.8

I 19.6

106.4

172.9

210.2

313.6

247.5

of Time after Q (m3/secl E(mg/m3) marker Flow of river injection (b)

3.9

6.7

7.9

9.1

11.1

14.3

17. I

17.6

23.0

32.5

~37.9

38.8

35.3

38, I

36.2

61.7

59.9

51.3

61.9

102.5

86.8

100.7

127.4

216.6

177.0

400.01 )

400.01 )

400.01 )

400.01)

-

M(mg/m 3)

613

891

1086

967

1024

927

326

380

809

530

529

544

481

647

6t9

360

334

195

361

487

363

474

375

322

351

251

305

455

359

0.0313. 106

0.0658. 106

0.0888. 106

0.0934.106

0.0913. 106

0.100.106

0.0424. 106

0.0498. 106

0.146.106

0.221 . 106

0.247. 106

0.262.106

0.225.106

0.298.106

0.295.106

0.228.106

0.190.106

0.0759. 106

0.200.106

0.412.106

0.319.106

0.411 . 106

0.361 . 106

0.390.106

0.370.106

0.413.106

0.413.106

0.406.106

0.377.106

CI 3 (I) AUC(soe.mg/m 3) (m /sec) E.Q/M

6387

3038

2251

2141

2191

1993

4723

4016

1366

906

810

765

889

671

679

876

1055

2635

1002

486

627

486

554

513

541

485

484

492

530

CI (2) (m3/sec) LJAUC

I) estimated; Load of sodium fluoresceine (L): 200 kg (= 200.106 mg); Marker point: Rheinau, power station, lower part at water backflow, Rhine-km 58.8; Marker time: 18 Juli 1989 03.00 a.m.

84.7 97. I

Slckingen (power station)

Augst (power station)

70.5

Laufenburg (power station)

Riburg (power station)

50.1 63.2

AlbbnJck (power station, overflow, closed)

50.1

34.7

Zurzach (bridge, left)

50.1

31.3

Reckingen (power station, below)

Albbruek (power station, chanel right)

31,3

Reckingen (power station, above)

Albbruek (power station, ehanel left)

24.1 24.1

24.1

Kaiserstuhl (bridge, middle left)

Kaiserstuhl (bridge, right)

24.1

Kaiserstuhl (bridge, left)

Kaiserstehl (bridge, middle right)

19.9 19.9

Eglisau (power station, below)

19.9

Eglisau (power station, entrance turbines)

Eglisau (power station, overflow)

15.7

Eglisau (bridge, right)

7.4

15.7

8.3

Rfutlingen(bridge, right)

15.7

8.3

Rfullingen(bridge, middle right)

Eglisau (bridge, left)

8.3

R~lliagen (bridge. middle left)

Eglisau (bridge, middle)

8.3

8.3

R~llingen (bridge, left)

8.3

Distance to Length marker point Segment (kin) (kin)

Clearance of sodium fluoresceine from the river Rhine (July 1989)

Samplingpomt

Table 3

-~

416 The binding of a drug to proteins in the human body can be compared to the binding of a xenobiotic to solid particles or to the sediment in a river. However, the concentrations in both systems are quite different. The concentration of albumin in blood plasma ranges between 35 - 55 g/l. As an example, after ingestion of a tablet of 400 mg of the antiinflammatory drug ibuprofen maximal drug concentrations after 1 to 2 hours reach 15 - 25 mg/1 blood serum. Protein binding of ibuprofen in blood is about 99 %. In contrast, the concentration of sodium fluoresceine in the rivers Aare and Rhine are three orders of magnitude lower than blood serum levels of ibuprofen. Also the concentration of solid particles in the river is lower than the concentration of albumin in blood plasma. Particle binding of sodium fluoresceine is probably lower than protein binding of ibuprofen. It is assumed that only a small fraction of sodium fluoresceine is metabolized during the 1 to 2 days of the experiment in the rivers and that the parent compound sodium fluoresceine was measured during the experiment. In conclusion the data support the idea that the clearance concept used in medicine all over the world can also be applied to get the clearance of xenobiotics from rivers. Such a clearance can be calculated by two methods using E.Q/M or IYAUC, respectively. More data are necessary to further evaluate the concept. It can be used to compare the clearance of different xenobiotics from the same river or to compare the clearance of the same xenobiotic from different rivers, provided that the results of more field experiment of this kind become available. Such an approach is model independent and rather easy to perform. Furthermore, it reduces a whole set of field data to a single figure the clearance value -, which could help scientists as well as administrators of regulating agencies to interpret data from xenobiotics.

417

Acknowledgement The help of Dr. Franz Bachmann and M. Kiener, School of Engineering Burgdorf, Switzerland with the computer program MATHLAB is very appreciated.

REFERENCES 1. Bradley, S.E., 1987. Clearance concept in renal physiology. In Renal Physiology: People and Ideas. Ed. C.W. Gottschalk, R.W. Berliner and G.H. Giebisch, American Physiological Society, Bethesda MD; Waverly Press, Williams and Williams Co., Baltimore MD, pp. 63-100. 2.

Rowland, M., Benet, L.Z. and Graham, G.G., 1973. Clearance concepts in pharmacokinetics. J. Pharmacokin. Biopharm., 1, 123-136.

3,

Klotz, U., 1984. Klinische Pharmakokinetik. Gustav Fischer Verlag, Stuttgart, New York

4.

Moeller, E., Mclntosh, J.F., and Van Slyke, D.D., 1928. Studies of urea excretion. II. Relationship between urine volume and the rate of urea excretion by normal adults. J. Clin. Invest., 6, 427 - 465. St~ihler, M., 1994. Modellunabh~ngige Okotox., 6, 199-203.

Analyse in der Okotoxikologie. UWSF-Z Umweltchem.

6.

Karlaganis, G., and Bradley, S.E., 1992. Soil atrazine clearance: application of a physiologic and clinical pharmacologic approach in environmental science. Chemosphere, 24, 1645-1652.

7.

Hari, T., von Arx, R., Ammon, H.U., and Karlaganis, G., 1996. Clearance of atrazine in soil describing xenobiotic behaviour. ESPR-Environ.Sci. Pollut. Res., 3, 32-38.